Persistent olfactory learning deficits during and post-COVID-19 infection

Quantifying olfactory impairments can facilitate early detection of Coronavirus disease 2019 (COVID-19). Despite being a debated topic, many reports provide evidences for the neurotropism of SARS-CoV-2. However, a sensitive, specific, and accurate non-invasive method for quantifying persistent neurological impairments is missing to date. To quantify olfactory detectabilities and neurocognitive impairments in symptomatic COVID-19 patients during and post-infection periods, we used a custom-built olfactory action meter (OAM) providing accurate behavioural readouts. Ten monomolecular odors were used for quantifying olfactory detectabilities and two pairs of odors were employed for olfactory matching tests. We followed cohorts of healthy subjects, symptomatic patients, and recovered subjects for probing olfactory learning deficits, before the Coronavirus Omicron variant was reported in India. Our method identifies severe and persistent olfactory dysfunctions in symptomatic patients during COVID-19 infection. Symptomatic patients and recovered subjects showed significant olfactory learning deficits during and post-infection periods, 4–18 months, in comparison to healthy subjects. On comparing olfactory fitness, we found differential odor detectabilities and olfactory function scores in symptomatic patients and asymptomatic carriers. Our results indicate probable long-term neurocognitive deficits in COVID-19 patients imploring the necessity of long-term tracking during post-infection period. Differential olfactory fitness observed in symptomatic patients and asymptomatic carriers demand probing mechanisms of potentially distinct infection routes. Graphical Image 1

Persistent olfactory learning deficits during and post-COVID-19 infection.

Quantifying olfactory impairments can facilitate early detection of Coronavirus disease 2019 (COVID-19). Despite being a debated topic, many reports provide evidence for the neurotropism of SARS-CoV-2. However, a sensitive, specific, and accurate non-invasive method for quantifying persistent neurological impairments is missing to date. To quantify olfactory detectabilities and neurocognitive impairments in symptomatic COVID-19 patients during and post-infection periods, we used a custom-built olfactory-action meter (OAM) providing accurate behavioral readouts. Ten monomolecular odors were used for quantifying olfactory detectabilities and two pairs of odors were employed for olfactory matching tests. We followed cohorts of healthy subjects, symptomatic patients, and recovered subjects for probing olfactory learning deficits, before the Coronavirus Omicron variant was reported in India. Our method identifies severe and persistent olfactory dysfunctions in symptomatic patients during COVID-19 infection. Symptomatic patients and recovered subjects showed significant olfactory learning deficits during and post-infection periods, 4-18 months, in comparison to healthy subjects. On comparing olfactory fitness, we found differential odor detectabilities and olfactory function scores in symptomatic patients and asymptomatic carriers. Our results indicate probable long-term neurocognitive deficits in COVID-19 patients imploring the necessity of long-term tracking during post-infection period. Differential olfactory fitness observed in symptomatic patients and asymptomatic carriers demand probing mechanisms of potentially distinct infection routes.

Quantitative assessment of olfactory dysfunction accurately detects asymptomatic COVID-19 carriers.

BACKGROUND: COVID-19 threatens the global community because a large fraction of infected people are asymptomatic, yet can effectively transmit SARS-CoV-2. Finding and isolating these silent carriers is a crucial step in confining the spread of the disease. A sudden loss of the sense of smell has been self-reported by COVID-19 patients across different countries, consistent with expression of the molecular factors mediating SARS-CoV-2 uptake into human olfactory epithelial supporting cells. However, precise quantification of olfactory loss in asymptomatic COVID-19 carriers is missing to date. METHODS: To quantify olfactory functions in asymptomatic COVID-19 patients, we designed an olfactory-action meter that determines detectability indices at different odor concentrations and an olfactory matching accuracy score using monomolecular odors. The optimization of test parameters allowed us to reliably and accurately assess olfactory deficits in a patient within 20 minutes. FINDINGS: Measurement of detection indices at low concentrations revealed a 50% reduction in asymptomatic COVID-19 carriers. Further, patients with better detection scores showed significantly reduced olfactory matching accuracies compared to normal healthy subjects. Our quantification of olfactory loss, considering all parameters, identified 82% of the asymptomatic SARS-CoV-2 carriers with olfactory deficits. However, on subjective evaluation, only 15% of the patients noticed a compromised ability to smell. INTERPRETATION: Compromised olfactory fitness can serve as a strong basis for identifying asymptomatic COVID-19 patients. Detailed design specifications and protocols provided here should enable the development of a sensitive, fast, and economical screening strategy that can be administered to large populations to prevent the rapid spread of COVID-19. FUNDING: This work was supported by the DBT - Wellcome Trust India Alliance intermediate grant (IA/I/14/1/501,306 to N.A.) and UGC NET Fellowship (A.B.). All the funding sources played no roles in the study.